Marked differences in local bone remodeling in response to different marrow stimulation techniques in a large animal

Marrow stimulation, including subchondral drilling and microfracture, is the most commonly performed cartilage repair strategy, whereby the subchondral bone plate is perforated to release marrow-derived cells into a cartilage defect to initiate repair. Novel scaffolds and therapeutics are being designed to enhance and extend the positive short-term outcomes of this marrow stimulation. However, the translation of these newer treatments is hindered by bony abnormalities, including bone resorption, intralesional osteophytes, and bone cysts, that can arise after marrow stimulation. In this study, three different marrow stimulation approaches, microfracture, subchondral drilling, and needle-puncture, were evaluated in a translationally relevant large animal model, the Yucatan minipig. The objective of this study was to determine which method of marrow access (malleted awl, drilled Kirschner wire, or spring-loaded needle) best preserved the underlying subchondral bone. Fluorochrome labels were injected at the time of surgery and 2 weeks post-surgery to capture bone remodeling over the first 4 weeks. Comprehensive outcome measures included cartilage indentation testing, histological grading, microcomputed tomography, and fluorochrome imaging. Our findings indicated that needle-puncture devices best preserved the underlying subchondral bone relative to other marrow access approaches. This may relate to the degree of bony compaction occurring with marrow access, as the Kirschner wire approach, which consolidated bone most, induced the most significant bone damage with marrow stimulation. This study provides basic science evidence in support of updated marrow stimulation techniques for preclinical and clinical practice.

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Marked differences in local bone remodelling in response to different marrow stimulation techniques in a large animal

10.22203/ecm.v041a35 ◽

2021 ◽

Vol 41 ◽

pp. 546-557

Author(s):

HM Zlotnick ◽

◽

RC Locke ◽

BD Stoeckl ◽

JM Patel ◽

...

Keyword(s):

Subchondral Bone ◽

Bone Remodelling ◽

Scientific Evidence ◽

Kirschner Wire ◽

Large Animal Model ◽

Large Animal ◽

Needle Puncture ◽

Marrow Stimulation ◽

Post Surgery ◽

Local Bone

Marrow stimulation, including subchondral drilling and microfracture, is the most commonly performed cartilage repair strategy, whereby the subchondral bone plate is perforated to release marrow-derived cells into a cartilage defect to initiate repair. Novel scaffolds and therapeutics are being designed to enhance and extend the positive short-term outcomes of this marrow stimulation. However, the translation of these newer treatments is hindered by bony abnormalities, including bone resorption, intralesional osteophytes, and bone cysts, that can arise after marrow stimulation. In this study, three different marrow stimulation approaches – microfracture, subchondral drilling and needle-puncture – were evaluated in a translationally relevant large-animal model, the Yucatan minipig. The objective of the study was to determine which method of marrow access (malleted awl, drilled Kirschner wire or spring-loaded needle) best preserved the underlying subchondral bone. Fluorochrome labels were injected at the time of surgery and 2 weeks post-surgery to capture bone remodelling over the first 4 weeks. Comprehensive outcome measures included cartilage indentation testing, histological grading, microcomputed tomography and fluorochrome imaging. Findings indicated that needle-puncture devices best preserved the underlying subchondral bone relative to other marrow access approaches. This may relate to the degree of bony compaction occurring with marrow access, as the Kirschner wire approach, which consolidated bone the most, induced the most significant bone damage with marrow stimulation. This study provided basic scientific evidence in support of updated marrow stimulation techniques for preclinical and clinical practice.

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Composite biomaterial repair strategy to restore biomechanical function and reduce herniation risk in an ex vivo large animal model of intervertebral disc herniation with varying injury severity

PLoS ONE ◽

10.1371/journal.pone.0217357 ◽

2019 ◽

Vol 14 (5) ◽

pp. e0217357 ◽

Cited By ~ 5

Author(s):

Warren W. Hom ◽

Melanie Tschopp ◽

Huizi A. Lin ◽

Philip Nasser ◽

Damien M. Laudier ◽

...

Keyword(s):

Animal Model ◽

Intervertebral Disc ◽

Disc Herniation ◽

Injury Severity ◽

Ex Vivo ◽

Large Animal Model ◽

Intervertebral Disc Herniation ◽

Large Animal ◽

Repair Strategy

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No effect of platelet-rich plasma as adjuvant to bone marrow stimulation for the treatment of chondral defects in a large animal model

Archives of Orthopaedic and Trauma Surgery ◽

10.1007/s00402-019-03292-7 ◽

2019 ◽

Vol 140 (1) ◽

pp. 77-84 ◽

Cited By ~ 1

Author(s):

Morten Lykke Olesen ◽

Bjørn Borsøe Christensen ◽

Casper Bindzus Foldager ◽

Kris Chadwick Hede ◽

Natasja Leth Bergholt ◽

...

Keyword(s):

Bone Marrow ◽

Animal Model ◽

Platelet Rich Plasma ◽

Large Animal Model ◽

Large Animal ◽

Bone Marrow Stimulation ◽

Marrow Stimulation ◽

Chondral Defects

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Radiologic evaluation using computed tomography for compensatory lung growth; a prospective comparison with histological data from a large animal model

10.21203/rs.3.rs-498601/v1 ◽

2021 ◽

Author(s):

Keiji Ohata ◽

Toyofumi F. Chen-Yoshikawa ◽

Masatsugu Hamaji ◽

Takeshi Kubo ◽

Tatsuo Nakamura ◽

...

Keyword(s):

Computed Tomography ◽

Lung Resection ◽

Large Animal Model ◽

Large Animal ◽

Lung Growth ◽

Lung Weight ◽

Tissue Volume ◽

Compensatory Lung Growth ◽

Post Surgery ◽

Ct Data

Abstract Background Non-invasive analysis using computed tomography (CT) data may be a promising candidate to evaluate neo-alveolarization in adult lungs following lung resection. This study evaluates and compares the validity of CT analysis with histologic morphometry for compensatory lung growth in a large animal model.Methods We calculated the radiologic tissue volume and the radiologic lung weight from CT data taken at 1, 3, and 6 months post-surgery on 15 male beagle dogs that had a right thoractotomy, bilobectomy, or pneumonectomy (n = 5 in each group). Results were analyzed using one-way ANOVA and were subsequently compared to histologic findings of tissue samples at 6 months post-surgery using Pearson’s correlation.Results An increase in radiologic tissue volume and radiologic lung weight was identified, which was positively correlated with histologic lung parenchymal amounts (correlation coefficient = 0.955 and 0.934, respectively, p < 0.001). Histology of lung specimens at six months post-surgery revealed an increase in the tissue amount in both Bilobectomy and Peumonectomy groups, which was consistent with compensatory lung growth.Conclusion Radiologic tissue volume and radiologic lung weight reflected compensatory lung growth following lung resection. Radiologic assessment using CT data can be a promising clinical modality to evaluate postoperative lung growth.

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Early-stage Pathogenic Sequence of Jaw Osteoradionecrosis in vivo

Journal of Dental Research ◽

10.1177/0022034512448661 ◽

2012 ◽

Vol 91 (7) ◽

pp. 702-708 ◽

Cited By ~ 19

Author(s):

J. Xu ◽

Z. Zheng ◽

D. Fang ◽

R. Gao ◽

Y. Liu ◽

...

Keyword(s):

Blood Flow ◽

Bone Remodeling ◽

Tooth Extraction ◽

Early Stage ◽

Morphological Changes ◽

Large Animal Model ◽

Large Animal ◽

Local Blood Flow ◽

Early Stages

The mechanism underlying jaw osteoradionecrosis (ORN) is not fully understood, particularly in the early stages. To investigate bone and vessel pathogenesis in the early stages of jaw ORN, we generated a mandibular ORN model in miniature pigs (minipigs) by applying a combination of single-dose 25-Gy irradiation (IR) and tooth extraction. We studied 6 ORN model minipigs and 6 control, non-irradiated minipigs. We measured dynamic morphological changes, bone-remodeling-associated gene expression, sphingomyelinase activity, and local blood flow. Bone remodeling, including bone resorption and new bone formation, was observed within 15 days post-IR. Later, an ORN-related imbalance in bone metabolism gradually occurred, with loss of bone regeneration capacity, collagen collapse, and microvascular obliteration. Within 24 hrs post-IR, sphingomyelinase significantly increased in irradiated tissues. At 1 wk post-IR, local blood flow increased, but at 15 days post-IR, it significantly decreased to 50% below normal levels. This study provided details of the sequential occurrences in early-stage ORN in a large animal model. Our results suggested that reduced local blood flow and consequent hypovascularity may have caused an imbalance in bone remodeling. This suggested that microvessel damage may play a key role in the initiation of ORN.

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